The present invention relates to an iron preparation suitable for use in mammals and to a process for the manufacture of such preparations. More paticularly, the present invention relates to the complexes formed by iron and an activated polymeric polyhydroxy compound.
It has heretofore been known to use an iron-dextran complex to increase reproduction at pig breed by counteracting the development of anemia at an early stage, (Andersson N. S. E., Acta med. scand. 138 (1950) suppl. 241.1-17).
It is well known that a number of polyvalent metallic ions such as iron will form complexes with polyhydroxy compounds such as polyhydric alcohols. However, on any substantial change in pH, the shift in equilibrium may cause the complex to decompose and the metallic ion in the presence of hydroxyl ion may tend to form a precipitate. This materially reduces the usefulness of these complexes for holding metallic ions in solution over varying pH ranges, and accordingly limits the usefulness of such complexes for trace metal metabolism in the body of mammals, including the human body.
In the preparation of iron complexes, it is known that the iron should be in the trivalent form since ferrous compounds do not give the desired stability of the ferric compounds. Ferric chloride is commonly utilized as a source for ferric ions. However, since ferric chloride is difficult to handle because it is corrosive to the conventional metal containers utilized in large scale operations, it presents certain disadvantages. Furthermore, in the conventional process of preparing iron-dextran complexes, precipitants, such as methanol, ethanol, isopropanol, acetone and methylethyl ketone are utilized in order to isolate and obtain the desired product which undergoes still further isolation and purification processes to obtain a suitable compound for use as an injectable.
U.S. Pat. No. 2,885,393 discloses the preparation of dextran-iron complexes utilizing either a hydrolysis mixture of dextran of fractionated dextran.
U.S. Pat. No. 3,574,184 discloses a process wherein colloidal ferric hydroxide is preformed under controlled conditions and then reacted with dextrans to form a ferric hydroxide-dextran complex.
U.S. Pat. No. 2,820,740 discloses a method for forming hydrogenated dextrans and the formation of ferric hydroxide - partially depolymerized dextran complexes.
U.S. Pat. No. 3,151,107 discloses a process for preparing carboxy alkyl dextrans and the preparation of water soluble iron complexes of the carboxy alkyl dextrans.
The dextrans and dextrins of such an average molecular weight are obtained by known methods, such as by growing under carefully controlled conditions of temperature, appropriate organisms in a suitable nutrient medium containing a high proportion of sucrose or by controlled acid hydrolysis of native dextrans and dextrins or they may be obtained synthetically, as described for instance in U.S. Pat. No. 3,022,221 and Rompp Chemielexikon, 4th edition, 1958, column 1121-1122.
The hydrogenated dextrans and dextrins may be produced according to known methods, such as by subjecting a dextran or dextrin of the average molecular weight defined hereinabove to reaction with sodium boro-hydride in an aqueous medium or by catalytic hydrogenation as described for instance in U.S. Pat. Nos. 2,807,610 or 3,022,221 or in J. Am. Chem. Soc. 74 (1952) pgs. 2126-2127.
Algin is a polysaccharide which is nearly a pure polymer of uronic acid arranged in a long linear chain, and is unique among the water soluble gums. The principal source of algin is Macrosystis Pyrifers, a giant kelp. The most common algin compound is sodium alginate. The modern mechanized algin processing plant meets the requirements of the Food, Pharmaceutical and Industrial Users for a pure, clean uniform water soluble gum. Pharmaceutical grades of alginate are entirely free of cellulose, form water soluble salts with various metals, and have been used as suspending agents and as protective colloids in many pharmaceuticals. In some systems, such as those containing penicillin, sulfa drugs and colloidal sulfur, they provide exceptional stability because of their action as protective colloids.